title: Phase I study of sunitinib plus capecitabine/cisplatin or capecitabine/oxaliplatin in advanced gastric cancer.
abstract: BACKGROUND
  We evaluated the maximum tolerated dose (MTD) and safety of sunitinib plus capecitabine/cisplatin (XP) or capecitabine/oxaliplatin (XELOX) in Korean patients with advanced gastric cancer (GC).
  
  
  METHODS
  Sunitinib (37.5 or 25 mg/day) was administered on a 2-week-on/1-week-off schedule with chemotherapy. Assessments included dose-limiting toxicity (DLT), safety, pharmacokinetics, and antitumor activity.
  
  
  RESULTS
  Twenty-eight patients received sunitinib/XP; 48 received sunitinib/XELOX. The MTDs were: sunitinib 25 mg/day, cisplatin 80 mg/m(2), and capecitabine 1,000 mg/m(2); sunitinib 37.5 mg/day, oxaliplatin 110 mg/m(2), and capecitabine 800 mg/m(2); and sunitinib 25 mg/day, oxaliplatin 110 mg/m(2), and capecitabine 1,000 mg/m(2). DLTs at the MTDs comprised grade (G) 4 febrile neutropenia plus G3 diarrhea (n = 1; sunitinib/XP), dose delays due to hematologic toxicity (n = 2; both sunitinib/XP), G3 bleeding (menorrhagia; n = 1; sunitinib/XELOX), and G3 increased alanine aminotransferase levels (n = 1; sunitinib/XELOX). There was a high frequency of G3/4 hematologic adverse events observed with both treatment regimens, particularly with sunitinib/XP. Frequent non-hematologic, G3/4 adverse events were nausea, stomatitis, and hypophosphatemia with sunitinib/XP and hypophosphatemia and pulmonary embolism with sunitinib/XELOX. No drug-drug interactions were apparent. At the MTDs, median progression-free survival was 6.4 months and 5.5-8.0 months for sunitinib/XP and sunitinib/XELOX, respectively; and the objective response rate was 46.7% and 43.5-45.5% for sunitinib/XP and sunitinib/XELOX, respectively.
  
  
  CONCLUSIONS
  At the MTD, sunitinib/XELOX had an acceptable safety profile in patients with advanced GC.
authors.affiliation: Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: K-W
authors.initials: KW
authors.lastname: Lee
authors.forename: S R
authors.initials: SR
authors.lastname: Park
authors.forename: D-Y
authors.initials: DY
authors.lastname: Oh
authors.forename: Y-I
authors.initials: YI
authors.lastname: Park
authors.forename: R
authors.initials: R
authors.lastname: Khosravan
authors.forename: X
authors.initials: X
authors.lastname: Lin
authors.forename: S-Y
authors.initials: SY
authors.lastname: Lee
authors.forename: E-J
authors.initials: EJ
authors.lastname: Roh
authors.forename: O
authors.initials: O
authors.lastname: Valota
authors.forename: M J
authors.initials: MJ
authors.lastname: Lechuga
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Bang
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000069287:Capecitabine; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D011758:Pyrroles / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000097:blood / Q000188:drug therapy*; D000077210:Sunitinib
chemical_list: D007211:Indoles; D009944:Organoplatinum Compounds; D011758:Pyrroles; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D002945:Cisplatin; D005472:Fluorouracil; D000077210:Sunitinib